scholarly journals Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation

2021 ◽  
Author(s):  
Katherine B. Landmesser ◽  
Elizabeth B. Autry ◽  
Brian M. Gardner ◽  
Katherine A. Bosko ◽  
Aric Schadler ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Serum Concentration ◽  
Predictive Value ◽  
Area Under The Curve ◽  
Pulmonary Exacerbation ◽  
Maximum Serum ◽  
Curve Versus ◽  
Maximum Serum Concentration

scholarly journals Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation

2021 ◽  
Author(s):  
Katherine Landmesser ◽  
Elizabeth Autry ◽  
Brian Gardner ◽  
Katherine Bosko ◽  
Aric Schadler ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Predictive Value ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Primary Objective ◽  
Pulmonary Exacerbation ◽  
University Of Kentucky ◽  
Post Dose ◽  
Therapeutic Success ◽  
Maximum Serum

OBJECTIVES: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24) versus maximum concentration (Cmax) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. METHODS: A retrospective review was conducted in patients aged at least one month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019 . Patients were excluded if they had no growth of PsA on sputum culture or if two post-dose tobramycin levels were not obtained following a dose adjustment of ≥20%. RESULTS: A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n=91), 75.8% had an AUC24 ≥80 and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration (MIC). There was a significant correlation between AUC24 and Cmax (r2 = 0.727; p<0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 hours (50% versus 28.7%; p=0.047). CONCLUSIONS: The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multi-daily dosing of IV tobramycin should be used only in select pediatric and adult patients with CF.

Concentration of Glutethimide and Associated Compounds in Human Serum and Cerebrospinal Fluid After Drug Overdose

1974 ◽  
Vol 20 (2) ◽  
pp. 195-199 ◽  
Author(s):  
Martin Gold ◽  
Ernest Tassoni ◽  
Michael Etzl ◽  
George Mathew
Keyword(s):  
Gas Chromatography ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Serum Concentration ◽  
Human Serum ◽  
Drug Overdose ◽  
Gas Liquid Chromatography ◽  
Maximum Serum ◽  
Maximum Serum Concentration ◽  
Maximal Serum Concentration

Abstract Serum and cerebrospinal fluid of patients in coma owing to glutethimide overdose was assayed for glutethimide and associated compounds. The sample was extracted with chloroform and the extract assayed by gas-liquid chromatography on a column of "3% OV-17." Up to six constituents were found in serum in addition to glutethimide, only three of which were ever present in substantial quantity. The peaks seen on gas chromatography were numbered in order of elution. Glutethimide was peak No. 2. Peak No. 1 usually reached a maximum serum concentration in 10 or less hours, as did peak No. 4. Peak No. 3 reached a maximal serum concentration in 10 h or sooner also, but at 20 h the amount had changed little in most patients. Ambre and Fischer [Res. Commun. Pathol. Pharmacol. 4, 307 (1972)] speculate that peak No. 3 plays an important role in maintaining coma. Neither the pattern of change nor the relative concentrations in serum or cerebrospinal fluid on waking support their hypothesis.

Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis

2004 ◽  
Vol 24 (5) ◽  
pp. 447-453 ◽  
Author(s):  
Sharon M. Yeung ◽  
Scott E. Walker ◽  
Sandra A.N. Tailor ◽  
Linda Awdishu ◽  
Sheldon Tobe ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Serum Concentration ◽  
Empirical Treatment ◽  
Klebsiella Species ◽  
Maximum Serum ◽  
Gram Negative ◽  
E Coli ◽  
Continuous Cycling ◽  
Maximum Serum Concentration ◽  
Oral Ciprofloxacin

Background In order to avoid aminoglycosides, the International Society for Peritoneal Dialysis recommends cefazolin and ceftazidime for empirical treatment of peritonitis. Ciprofloxacin covers relevant gram-negative pathogens without the resistance associated with ceftazidime. However, ciprofloxacin pharmacokinetic data in patients on continuous cycling peritoneal dialysis (CCPD) are lacking. Objectives ( 1 ) To determine the pharmacokinetics of oral ciprofloxacin in CCPD patients, ( 2 ) to compare serum and dialysate ciprofloxacin concentrations with minimum inhibitory concentrations (MIC) of the gram-negative bacteria associated with peritonitis, and ( 3 ) to establish oral ciprofloxacin dosing guidelines for the empirical treatment of peritonitis in patients receiving CCPD. Methods Eligible CCPD patients received 2 doses of ciprofloxacin: 750 mg orally every 12 hours. Serial blood and end-of-dwell dialysate samples were collected during the first 12-hour interval; an end-of-dwell dialysate sample from the overnight dwell and a final blood sample were collected at the end of the second 12-hour interval. Ciprofloxacin concentrations were determined using a liquid chromatographic (HPLC)-fluorescence method. Pharmacokinetic calculations were completed assuming a one-compartment model. Results Eight patients completed the study. The pharmacokinetic parameters determined for ciprofloxacin were (mean ± SEM) serum half-life 10.1 ± 1.2 hours, maximum serum concentration 2.7 ± 0.5 mg/L, time to maximum serum concentration 1.6 ± 0.1 hours after the first dose, and peritoneal clearance 1.2% ± 0.1% of the mean calculated total body clearance. While all patients achieved serum area under the concentration-time curve: MIC > 125 for Escherichia coli and Klebsiella species after the first dose, only 2 patients achieved this goal for Pseudomonas aeruginosa. End-of-dwell dialysate concentrations were above the MIC for E. coli, Klebsiella spp, and P. aeruginosa after the second dose. Conclusion Ciprofloxacin 750 mg orally every 12 hours in CCPD patients may be useful for empirical gram-negative coverage of CCPD peritonitis and for treatment of documented peritonitis caused by sensitive E. coli or Klebsiella species. While ceftazidime may be required for documented pseudomonal peritonitis, the oral ciprofloxacin regimen achieved adequate serum concentrations to treat systemic gram-negative infections caused by sensitive E. coli or Klebsiella species.

scholarly journals Bacterial Strain-to-Strain Variation in Pharmacodynamic Index Magnitude, a Hitherto Unconsidered Factor in Establishing Antibiotic Clinical Breakpoints

2009 ◽  
Vol 53 (12) ◽  
pp. 5181-5184 ◽  
Author(s):  
Alasdair P. MacGowan ◽  
Rosy Reynolds ◽  
Alan R. Noel ◽  
Karen E. Bowker
Keyword(s):  
Serum Concentration ◽  
Bacterial Pathogen ◽  
Pharmacodynamic Modeling ◽  
Human Pharmacokinetics ◽  
Maximum Serum ◽  
Clinical Breakpoints ◽  
Dose Ranging ◽  
Maximum Serum Concentration ◽  
The Relationship

ABSTRACT Antibiotic pharmacodynamic modeling allows variations in pathogen susceptibility and human pharmacokinetics to be accounted for when considering antibiotic doses, potential bacterial pathogen targets for therapy, and clinical susceptibility breakpoints. Variation in the pharmacodynamic index (area-under-the-concentration curve to 24 h [AUC24]/MIC; maximum serum concentration of drug in the serum/MIC; time the serum concentration remains higher than the MIC [T > MIC]) is not usually considered. In an in vitro pharmacokinetic model of infection using a dose-ranging design, we established the relationship between AUC24/MIC and the antibacterial effect for moxifloxacin against 10 strains of Staphylococcus aureus. The distributions of AUC24/MIC targets for 24-h bacteriostatic effect and 1-log, 2-log, and 3-log drops in bacterial counts were used to calculate potential clinical breakpoint values, and these were compared with those obtained by the more conventional approach of taking a single AUC24/MIC target. Consideration of the AUC24/MIC as a distribution rather than a single value resulted in a lower clinical breakpoint.

scholarly journals Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

2018 ◽  
Vol 23 (2) ◽  
pp. 159-163
Author(s):  
Kristi L. Higgins ◽  
Cady Noda ◽  
Jeremy S. Stultz
Keyword(s):  
Cystic Fibrosis ◽  
Primary Ciliary Dyskinesia ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Treatment Recommendation ◽  
Pharmacokinetic Parameters ◽  
Maximum Serum ◽  
First Case ◽  
Ciliary Dyskinesia

The pharmacokinetics of tobramycin in patients with ciliary dyskinesia have not been previously reported. A 10-year-old female patient with primary ciliary dyskinesia was admitted to the general pediatrics floor with an acute respiratory exacerbation after several months of worsening lung function that was unresponsive to oral antibiotics. Extrapolating from cystic fibrosis dosing regimens, she was given intravenous tobramycin 320 mg (10.3 mg/kg/day) on admission as a result of concern for a Pseudomonas aeruginosa infection. Two-point pharmacokinetic monitoring revealed a maximum serum concentration (Cmax) of 18.9 mg/L and a 24-hour area under the curve (AUC0–24hr) of 58.8 (mg × hr)/L, as well as a volume of distribution (Vd) of 0.5 L/kg and an elimination rate (Ke) of 0.34 hr−1. After a dosage increase to tobramycin 400 mg (12.8 mg/kg/day), pharmacokinetic parameters on 2 assessments were as follows: Vd 0.37 to 0.39 L/kg, Ke 0.33 to 0.39 hr−1, Cmax 27.8 to 28.7 mg/L, and AUC0–24h 78.4 to 89.4 (mg × hr)/L. This was the first case report of aminoglycoside pharmacokinetics in a patient with ciliary dyskinesia. The administration of larger doses (up to 12.8 mg/kg/day) of extended-interval tobramycin, similar to the treatment recommendation of at least 10 mg/kg/day for cystic fibrosis patients, was necessary in this patient to achieve serum concentrations that were appropriate for treatment.

scholarly journals Lung ultrasound for the diagnosis of cystic fibrosis pulmonary exacerbation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Hassanzad ◽  
Arda Kiani ◽  
Atefeh Abedini ◽  
Hoseinali Ghaffaripour ◽  
Habib Emami ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Predictive Value ◽  
Diagnostic Performance ◽  
Lung Ultrasound ◽  
Characteristic Curve ◽  
Cross Sectional Study ◽  
Pulmonary Exacerbation ◽  
High Resolution Computed Tomography ◽  
Cross Sectional ◽  
Pleural Thickening

Abstract Background High-resolution computed tomography (HRCT) is the gold standard for the evaluation of cystic fibrosis (CF) lung disease; however, lung ultrasound (LUS) is being increasingly used for the assessment of lung in these patients due to its lower cost, availability, and lack of irradiation. We aimed to determine the diagnostic performance of LUS for the evaluation of CF pulmonary exacerbation. Methods This cross-sectional study included patients with CF pulmonary exacerbation admitted to Masih Daneshvari Hospital, Tehran, Iran, from March 21, 2020 to March 20, 2021. Age, gender, and body mass index (BMI) of the patients were recorded. All patients underwent chest X-ray (CXR), HRCT, and LUS on admission. Pleural thickening, atelectasis, air bronchogram, B-line, and consolidation were noted in LUS and then compared with the corresponding findings in CXR and HRCT. Taking HRCT findings as reference, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA) of LUS and CXR for the detection of each pulmonary abnormality were determined. Results Of the 30 patients included in this study, with a mean age of 19.62 ± 5.53 years, 14 (46.7%) were male. Of the 15 patients aged 2–20 years, BMI was below the 5th percentile in 10 (66.7%), within the 5–10 percentiles in 1 (6.7%), 10–25 percentiles in 3 (20%), and 25-50 percentiles in 1 (6.7%). The mean BMI for 15 patients > 20 years was 18.03 ± 2.53 kg/m2. LUS had better diagnostic performance compared to CXR for the detection of air bronchogram, consolidation, and pleural thickening (area under the receiver operating characteristic curve [AUROC]: 0.966 vs. 0.483, 0.900 vs. 0.575, and 0.656 vs. 0.531, respectively). Also, LUS was 100% and 96.7% specific for the diagnosis of pleural effusion and atelectasis, respectively. Conclusions LUS appears to be superior to CXR and comparable with HRCT for the evaluation of CF pulmonary exacerbation, especially in terms of air bronchogram and consolidation detection. LUS can be used to lengthen the HRCT evaluation intervals in this regard or utilized along with HRCT for better evaluation of CF pulmonary exacerbation.

Adequacy of a hospital-wide standard dose of 7mg/kg bodyweight gentamicin sufficient to achieve an adequate prophylactic maximum serum concentration (Cmax) in burn patients undergoing surgical burn wound treatment

Burns ◽  
2016 ◽  
Vol 42 (8) ◽  
pp. 1819-1824 ◽  
Author(s):  
Lennaert C.P. Borra ◽  
Tessa M. Bosch ◽  
Margriet E. van Baar ◽  
Jan Dokter ◽  
Irma M. Oen ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Standard Dose ◽  
Burn Patients ◽  
Wound Treatment ◽  
Burn Wound ◽  
Maximum Serum ◽  
Maximum Serum Concentration

Comparative Bioavailability of Praziquantel Tablets

DICP ◽  
1989 ◽  
Vol 23 (1) ◽  
pp. 29-32 ◽  
Author(s):  
Sming Kaojarern ◽  
Surapol Nathakarnkikool ◽  
Uthai Suvanakoot
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Disintegration Time ◽  
Maximum Serum ◽  
British Pharmacopoeia ◽  
Elimination Half ◽  
Comparative Bioavailability ◽  
Maximum Serum Concentration

Six different brands of 600 mg praziquantel tablets were evaluated. In vitro studies demonstrated that all but one of the products met the British Pharmacopoeia 1980 disintegration time specifications. The comparative bioavailability of four of the internationally available brands of praziquantel tablets were then studied in eight healthy volunteers using a crossover design. Serum praziquantel levels were determined by high-performance liquid chromatography. Individual serum profiles were analyzed for pharmacokinetic parameters such as maximum serum concentration, time to reach maximum, and area under the curve. Following administration of praziquantel 40 mg/kg po, the mean peak serum concentrations and the time to reach the peak ranged from 1.007 to 1.625 μg/ml and from 1.72 to 2.81 hours, respectively. The elimination half-life of praziquantel was 1.15 (0.94–1.25) hours. Differences greater than 20 percent (p < 0.05) were noted for these parameters between the original brand and the generic formulations. The relative bioavailabilities of the generic praziquantel formulations, with respect to the original brand, were 91.25, 80.95, and 69.86 percent. This is due to the failure of disintegration and subsequently poor dissolution. The effect of 30 percent reduction of bioavailability may lead to unacceptably high rates of treatment failure.

Steady-State Pharmacokinetics of Oral Ciprofloxacin in Continuous Cycling Peritoneal Dialysis Patients: Brief Report

2018 ◽  
Vol 38 (1) ◽  
pp. 73-76
Author(s):  
Colin Lee ◽  
Sandra A.N. Walker ◽  
Lesley Palmay ◽  
Scott E. Walker ◽  
Sheldon Tobe ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Steady State ◽  
Serum Concentration ◽  
Half Life ◽  
Dialysis Patients ◽  
Maximum Serum ◽  
Continuous Cycling Peritoneal Dialysis ◽  
Continuous Cycling ◽  
Maximum Serum Concentration ◽  
Oral Ciprofloxacin

Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ±1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.

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